Thromboxane A.sub.2 receptor antagonists have been found to be effective in preventing early pulmonary hypertension induced by exposure to endotoxin, Schumacher, W. A. et al., "Effect of the TxA.sub.2 -receptor antagonists SQ 29,548 and SQ 28,688 on the pulmonary hypertensive response to endotoxemia in swine," Pharmacology 34:301-308, 1987.
Protamines are simple proteins of low molecular weight that are rich in basic amino acids. Protamine is a cationic protein which is used in man to reverse the anticoagulant activity of heparin. It reacts with anionic heparin to form a complex which is inactive as an anticoagulant.
Upon completion of surgical procedures requiring anticoagulant treatment, it is desirable to restore normal function to the blood coagulation cascade to minimize post-operative bleeding. When heparin is employed as the anticoagulant, protamine is often infused to neutralize the heparin-induced anticoagulant activity. Thus, protamine acts as a heparin antagonist and is used to neutralize heparin in surgical procedures.
Unfortunately, certain patients show intolerance to protamine. Adverse reactions which may result from the interaction between protamine and heparin include anaphylaxis and pulmonary hypertension. The latter response, when produced in pigs, can be significantly blunted by pretreatment with aspirin and is associated with enhanced TxB.sub.2 blood levels, Degges, R. D. et al., "Pulmonary hypertensive effect of heparin and protamine interaction; evidence for thromboxane B.sub.2 release from the lung," Am. J. Surg. 154:696-698, 1987. The Physicians' Desk Reference, 41st Edition, 1987, pp, 1162-1163, indicates that "Because fatal reactions often resembling anaphylaxis have been reported after administration of protamine sulfate, the drug should be given only when resuscitation techniques and treatment of anaphylactoid shock are readily available."